DESCRIPTION (Verbatim from the Applicant's Abstract): The purpose of this application is to develop a novel optical spectroscopy technique for detecting characteristics of atherosclerotic plaques of research and clinical interest, particularly unstable plaques. The overall goal is to determine spectroscopic characteristics of atherosclerotic plaques that can be correlated with pathological features of unstable plaques. While atherosclerosis is a lifelong progressive disease, clinical complications and death are primarily the result of sudden plaque rupture. Early diagnostic of unstable plaques is the key to improved treatment and survival rates of cardiovascular patients. The cause and the exact mechanism of plaque rupture are not well understood. Histopathological evidence suggests that composition of the plaque itself is an important predictor factor. We propose the Time-Resolved Laser-Induced Fluorescence Spectroscopy (TR-LIFS) technique as a tool for characterizing the composition of the arterial wall and for distinguishing unstable plaques. During progression, the biochemical composition and morphology of the atherosclerotic plaque changes leading to altered optical characteristics of the tissue. The proposed TR-LIFS system will obtain both spectral and time-resolved fluorescence information and combine the wealth of spectroscopic parameters for enhancing tissue characterization. Three specific aims will be addressed: 1) to build-up on the existing TR-LIFS technique and to determine the best methodology for utilizing this technique to characterize plaque in-vivo. This will be assessed by developing a portable TR-LIFS system capable of operating in in-vivo conditions and testing this new system in an animal atherosclerotic model. 2) To characterize in in-vivo and ex-vivo carotid artery plaque and to identify those spectroscopic features that may distinguish the unstable plaque. This will be accomplished by TR-LIFS measurements of carotid plaques in patients undergoing carotid endarterectomy and comparison of those findings to that of histopathological examination of the plaque. 3) To build-up on the existing algorithms/methods for time-resolved spectroscopy data analysis and to advance methods for lesions classification and features of instability identification. This will be assessed by investigating data analysis, statistical, and classification methods that can optimally use the wealth of spectroscopic parameters provided by TR-LIFS data. This research will provide a technique capable of detecting and monitoring compositional features of atherosclerotic lesion predictable of plaque rupture. This study will facilitate translation of research findings on carotid lesions into clinical practice for identifying and treating those patients who are more likely to have an unstable plaque.